Pretreatment drug for t cell infusion therapy for immune-checkpoint inhibitor-resistant tumor

Patent metadata

Field	Value
Publication number	US-2023201263-A1
Application number	US-202218071010-A
Country	US
Kind code	A1
Filing date	Nov 29, 2022
Priority date	Feb 8, 2016
Publication date	Jun 29, 2023
Grant date	—

Abstract

An antigen-loaded nanogel is formed by loading or encapsulating one or more long peptide antigens or one or more protein antigens in a hydrophobized polysaccharide. The long peptide antigen(s) or protein antigen(s) contains (or each contain) one or more CD8+ cytotoxic T cell recognition epitopes and/or one or more CD4+ helper T cell recognition epitopes, which is/are derived from the antigen. The antigen-loaded nanogel is administered at least one day prior to administration of antigen-specific T cells to improve the efficacy of a T cell infusion therapy against an immune checkpoint inhibitor-resistant tumor. The hydrophobized polysaccharide may be pullulan having cholesteryl groups bound thereto. An immune-enhancing agent also may be administered in or with the antigen-loaded nanogel.

First claim

1 - 13 . (canceled)

14 . A method for treating an immune checkpoint inhibitor-resistant tumor in a patient in need thereof, comprising:
administering to the patient a therapeutically effective amount of an antigen-loaded nanogel comprising a long peptide antigen or a protein antigen loaded in a hydrophobized polysaccharide, the long peptide antigen or protein antigen containing a CD8+ cytotoxic T cell recognition epitope and/or a CD4+ helper T cell recognition epitope, which is/are derived from an antigen of the immune checkpoint inhibitor-resistant tumor; and at least 1 day thereafter, administering to the patient a therapeutically effective amount of antigen-specific T cells that bind to an antigen of the immune checkpoint inhibitor-resistant tumor.

15 . The method according to claim 14 , further comprising administering an immune-enhancing agent with the antigen-loaded nanogel.

16 . The method according to claim 15 , wherein the immune-enhancing agent is contained in the antigen-loaded nanogel.

17 . The method according to claim 14 , wherein the antigen-specific T cell is a T cell that expresses a T cell receptor that recognizes the antigen or is a chimeric antigen receptor that recognizes the antigen.

18 . The method according to claim 14 , wherein the long peptide antigen or protein antigen is composed of 23 to 120 amino acid residues.

19 . The method according to claim 14 , wherein the long peptide antigen or protein antigen comprises a sequence selected from the group consisting of 2 to 10 tyrosines, 2 to 10 threonines, 2 to 10 histidines, 2 to 10 glutamines and 2 to 10 asparagines between the T cell recognition epitopes in the long chain peptide antigen.

20 . The method according to claim 14 , wherein the hydrophobized polysaccharide comprises pullulan and cholesteryl groups.

21 . The method according to claim 16 , wherein the immune-enhancing agent is at least one selected from the group consisting of TLR (Toll-like receptor) agonists (CpG oligoDNA or poly-IC RNA), STING agonists or RLR (RIG-I-like receptors) agonists.

22 . The method according to claim 14 , wherein said antigen is a tumor-specific antigen protein or a tumor stroma-specific antigen protein.

23 . The method according to claim 14 , wherein the antigen-loaded nanogel is administered according to an administration route selected from the group consisting of subcutaneous, intradermal, intramuscular, intratumoral and intravenous.

24 . The method according to claim 14 , wherein the antigen-loaded nanogel has a particle size of 80 nm or less and the hydrophobized polysaccharide contains pullulan and cholesteryl groups.

25 . The method according to claim 24 , wherein the antigen-loaded nanogel is administered according to an administration route selected from the group consisting of subcutaneous, intradermal, intramuscular, intratumoral and intravenous.

26 . The method according to claim 25 , wherein the antigen-specific T cell is a T cell that expresses a T cell receptor that recognizes the antigen or is a chimeric antigen receptor that recognizes the antigen.

27 . The method according to claim 26 , further comprising administering an immune-enhancing agent with the antigen-loaded nanogel.

28 . The method according to claim 27 , the long peptide antigen or protein antigen is composed of 23 to 120 amino acid residues.

29 . The method according to claim 28 , wherein the long peptide antigen or protein antigen comprises a sequence selected from the group consisting of 2 to 10 tyrosines, 2 to 10 threonines, 2 to 10 histidines, 2 to 10 glutamines and 2 to 10 asparagines between the T cell recognition epitopes in the long chain peptide antigen.

30 . The method according to claim 29 , wherein the immune-enhancing agent is at least one selected from the group consisting of TLR (Toll-like receptor) agonists (CpG oligoDNA or poly-IC RNA), STING agonists or RLR (RIG-I-like receptors) agonists.

31 . The method according to claim 30 , wherein said antigen is a tumor-specific antigen protein or a tumor stroma-specific antigen protein.

32 . The method according to claim 31 , wherein the long peptide antigen or protein antigen is derived from human NY-ESO-1.

33 . The method according to claim 14 , wherein the therapeutically effective amount of the antigen-specific T cells that bind to an antigen of the immune checkpoint inhibitor-resistant tumor are administered between 1 day and 2 weeks after the administration of the antigen-loaded nanogel.

Assignees

• Univ Mie
• Univ Kyoto

Inventors

• Shiku Hiroshi
• Harada Naozumi
• Muraoka Daisuke
• Akiyoshi Kazunari

Classifications

• A61K40/4251

  Kinases, e.g. Raf or Src · CPC title

• A61K40/32

  T-cell receptors [TCR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title

• A61K47/36 Primary

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title